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We examined whether cortical thickness in several brain regions confers resilience against cognitive decline in amyloid\u2010positive adults by moderating the effects of thinner cortex in Alzheimer's disease (AD)\u2010related brain regions and of higher levels of tau.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Amyloid\u2010positive participants from the Alzheimer's Disease Neuroimaging Initiative with relevant imaging data were included (n\u2009=\u2009160, observations\u2009=\u2009473). Risk factors included an AD brain signature and cerebrospinal fluid phosphorylated tau. Cognitive measures were episodic memory and executive function composites. Mixed effects models tested whether region\u2010specific cortical thickness moderated relationships between markers of AD risk and memory or executive function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cross\u2010sectionally, thicker cortex in 8 regions minimized the negative impact of thinner cortex\/smaller volume in AD signature regions on executive function. Longitudinally, higher baseline thickness in a composite of these 8 regions predicted less memory decline (<jats:italic>p<\/jats:italic>\u2009=\u20090.007) and weakened negative effects of phosphorylated tau on memory decline (<jats:italic>p<\/jats:italic>\u2009=\u20090.014), independent of baseline cognition and risk markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>We identified 8 cortical regions that appear to confer cognitive resilience cross\u2010sectionally and longitudinally in the face of established indicators of AD pathology. Brain regions fostering executive function may enable compensation in later memory performance and confer cognitive resilience against effects of phosphorylated tau and AD\u2010related cortical changes. These \u201cresilience\u201d regions suggest the value of focusing on brain regions beyond only those determined to be AD\u2010related and may partially explain variability in AD\u2010related cognitive trajectories. 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